Ivabradine acts by inhibiting the ionic If current that modulates the pacemaker activity of sinoatrial node cells. The aim of present study is to evaluate the efficacy and safety of IvabRadine hemisulfate Sustained-release Tablets versus placebo in patients with moderate to severe chronic systolic heart failure.

Inclusion Criteria:

• aged from 18 to 75 years, males or females

• Willing to provide written informed consent

• NYHA Class II, III, or IV for≥4 weeks, in stable clinical condition for

  ≥4 weeks

• Optimized and unchanged chronic heart failure medications and dosages for≥4 weeks

• Sinus rhythm with resting heart rate≥70 b.p.m.

• Left-ventricular systolic dysfunction, with ejection fraction≥40% documented within previous 1 month

Exclusion Criteria:

• Unstable cardiovascular condition(for example, hospital admission for worsening heart failure)
• Recent (<2 months) myocardial infarction or recent or scheduled coronary revascularization
• Stroke or transient cerebral ischaemia within previous 4 weeks
• Severe primary valvular disease
• Scheduled surgery of valvular heart disease
• Active myocarditis
• Congenital heart diseases
• peripartum cardiomyopathy
• hyperthyroid heart disease
• On list for cardiac transplantation
• Cardiac resynchronization therapy started within previous 6 months
• Pacemaker with atrial or ventricular pacing (except biventricular pacing)˃40% of the time, or with stimulation threshold at the atrial or ventricular level˃60 b.p.m.
• Permanent atrial fibrillation or flutter
• Sick sinus syndrome, sinoatrial block, second and third degree atrio-ventricular block
• History of symptomatic or sustained (≥30 s) ventricular arrhythmia unless a cardioverter/defibrillator implanted
• Cardioverter/defibrillator shock within previous 6 months
• Family history or congenital long QT syndrome or treated with selected QT-prolonging products(except amiodarone)
• Contraindication or intolerance to ivabradine or lactulose
• Severe or uncontrolled hypertension (SBP≥180 mmHg or DBP≥110 mmHg)
• known anaemia(Hb<100 g/L)
• Known moderate or severe liver disease(ALT/AST˃3ULN), known severe renal disease(Cr˃2ULN)
• Pregnant or lactating women and women planning to become pregnant
• Use of an investigational drug within 30 days of enrollment
• Has a history of psychological illness/condition that interferes with ability to understand or complete requirements of the study